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Level 2 of 6Must-remember

Anaphylaxis: recognition and adrenaline

Assess, manage and stay safe — enough on its own

The card — assess, manage, caution

Assessment— look, ask, measure

  • The bedside triad: diagnose anaphylaxis in seconds from sudden onset with rapid progression, a life-threatening airway, breathing or circulation problem, and — in most but not all patients — skin or mucosal change.
  • History to ask for: what was eaten, injected, infused or stung, exactly when, and how long before symptoms began — parenteral exposures act within minutes and ingested ones within 30 minutes to 2 hours, and the shorter the interval the more severe the reaction is likely to be.
  • Ask about co-factors and risk: asthma and especially poorly controlled asthma (the single strongest predictor of a fatal outcome), beta-blockers including eye drops, ACE inhibitors, exercise, alcohol, NSAIDs, intercurrent infection, fatigue, and any previous reaction.
  • Skin and mucosa, present in over 90% of episodes: itch of the palms, soles and genitalia first, then flushing, sweating, conjunctival injection, generalised urticaria and angio-oedema of the lips, eyelids and oral mucosa — in deeply pigmented skin and poor light, palpate for weals rather than relying on inspection.
  • Airway, in this sequence: a lump-in-the-throat sensation, hoarseness or voice change, difficulty swallowing saliva, then inspiratory stridor, then obstruction, with visible progressive swelling of the tongue, soft palate and uvula — hoarseness is laryngeal oedema until proved otherwise.
  • Breathing: tachypnoea, wheeze, chest tightness, fatigue, cyanosis and falling oxygen saturation; bronchospasm dominates when the allergen has been inhaled and in a known asthmatic may be indistinguishable from an asthma attack.
  • Circulation: tachycardia, hypotension, faintness, a feeling of impending doom, drowsiness, syncope, arrhythmia and cardiac arrest — with warm flushed peripheries and a low jugular venous pressure, not the cold clammy skin of cardiogenic shock.
  • Gastrointestinal features are part of the syndrome: nausea, vomiting, crampy abdominal pain and diarrhoea may be the presenting complaint after an ingested trigger, and abdominal pain in a flushed hypotensive patient must not divert you towards a surgical diagnosis.
  • Measure and record: blood pressure, pulse, respiratory rate and oxygen saturation — in an adult, a systolic pressure below 90 mmHg or a fall of more than 30% from baseline defines hypotension.
  • The red flags to seek explicitly and repeatedly: hoarse or altered voice, inability to swallow saliva, visible tongue, palatal or pharyngeal swelling, inspiratory stridor, a silent chest or exhaustion in a wheezing patient, oxygen saturation below 92% despite supplemental oxygen, systolic blood pressure below 90 mmHg or a 30% fall, any reduction in conscious level, bradycardia in a shocked patient, and failure to improve after two doses of intramuscular adrenaline.
  • Grade severity simply (Brown): mild — skin and subcutaneous tissues only; moderate — respiratory, cardiovascular or gastrointestinal involvement (dyspnoea, stridor, wheeze, nausea, vomiting, diaphoresis, chest or throat tightness, abdominal pain); severe — cyanosis or SpO2 at or below 92%, systolic BP below 90 mmHg, confusion, collapse, loss of consciousness, incontinence.
  • The transition that matters is from skin-only disease to any objective airway, breathing or circulatory involvement — that is the point at which adrenaline becomes mandatory, and generalised urticaria alone is not anaphylaxis.
  • No rash in up to one patient in ten: cutaneous signs are frequently absent in explosive intravenous drug reactions, or appear only after resuscitation restores skin perfusion, so hypotension may be the sole feature; no rash never excludes the diagnosis.
  • In a child: blood pressure is preserved until late by vigorous vasoconstriction and tachycardia, so act on capillary refill, heart rate, conscious level, behaviour (he is not himself) and parental concern — waiting for hypotension is a recognised route to a paediatric death.
  • Under anaesthesia or sedation: the patient is draped and cannot complain, so unexplained hypotension, a rising airway pressure or a falling end-tidal carbon dioxide may be the only manifestation.
  • The mimics to consider: vasovagal syncope (pale, cold, clammy, bradycardic, recovers within seconds of lying flat), acute severe asthma, septic shock, cardiogenic shock or arrhythmia, pulmonary embolism, scombroid poisoning after dark-fleshed fish, panic attack or inducible laryngeal obstruction with normal saturations and blood pressure, and bradykinin-mediated angio-oedema — swelling without weals or itch, lasting over 24 hours, with a low C4 and no response to adrenaline or antihistamines.

Management— do this, in order

  • Stop the exposure in seconds: disconnect the offending infusion, blood component, antivenom or contrast at the cannula rather than merely closing the roller clamp, do not flush the line, and scrape a retained bee sting out sideways rather than grasping it — but if removing the trigger and giving adrenaline compete for time, adrenaline wins.
  • Lie the patient flat with the legs raised: sudden death has occurred in patients who were sat up, stood up or walked; if respiratory distress makes lying flat intolerable they may sit up but the legs stay raised, an unconscious breathing patient goes into the recovery position with legs raised, and after about 20 weeks of pregnancy into the left lateral position.
  • Adrenaline 1:1000 (1 mg/mL) intramuscularly into the anterolateral aspect of the middle third of the thigh (vastus lateralis), through clothing if necessary, with a needle long enough to reach muscle — at least 25 mm in an average adult; aspiration is unnecessary, and the thigh gives higher, faster peak concentrations than the deltoid.Doctor / Nurse
  • The dose by age: adult and child over 12 years 500 micrograms = 0.5 mL; 6–12 years 300 micrograms = 0.3 mL; 6 months–6 years 150 micrograms = 0.15 mL; under 6 months 100–150 micrograms = 0.1–0.15 mL — with a weight-based cross-check of 0.01 mg/kg to a maximum of 0.5 mg.Doctor / Nurse
  • Repeat after 5 minutes if the response is inadequate, and every 5 minutes thereafter for as long as the patient remains unwell; there is no maximum number of intramuscular doses, and patients are far more often harmed by too few than by too many.Doctor / Nurse
  • Where only 1:10 000 is stocked the intramuscular dose becomes 5 mL — a large, painful volume and a poor substitute; state the concentration, the volume and the route aloud before every injection.Doctor / Nurse
  • High-flow oxygen by reservoir mask at 15 L/min immediately and for as long as the emergency continues, targeting saturations of 94–98% once stability returns.
  • Fluid, delivered under pressure or by hand: 500–1000 mL of crystalloid (0.9% sodium chloride or a balanced solution such as Hartmann's) rapidly in an adult, escalating to 1–2 litres and beyond if hypotension persists, and 10 mL/kg boluses in a child reassessed after each — a bag hanging on a pole is not a fluid challenge, and adrenaline does not substitute for fluid nor fluid for adrenaline.Doctor / Nurse
  • Persisting wheeze after adrenaline is treated as acute asthma: nebulised salbutamol 5 mg (2.5 mg under 5 years), oxygen-driven and repeated as needed, with ipratropium bromide 500 micrograms (250 micrograms in children) added for severe bronchospasm; intravenous magnesium sulphate may be considered, remembering it is itself a vasodilator.
  • Upper airway oedema — nebulised adrenaline, oxygen-driven: 3 mg in an adult, or 1:1000 solution 0.5 mL/kg to a maximum of 5 mL in a child; it reduces mucosal swelling and buys time but does not secure an airway.Doctor / Nurse
  • Prepare early for a difficult airway if there is progressive hoarseness, inability to swallow saliva or visible pharyngeal swelling: the most experienced operator available, a smaller tube than usual, and equipment for front-of-neck access opened in advance.Doctor / NurseNot available at your setup — Endotracheal intubation kit.
  • Chlorphenamine, only after adrenaline: 10 mg by slow intravenous injection or intramuscularly in an adult and children over 12; 5 mg (6–12 years); 2.5 mg (6 months–6 years); 250 micrograms/kg (under 6 months). Alternatives are promethazine 25 mg by deep intramuscular injection in an adult, or diphenhydramine 1 mg/kg to a maximum of 50 mg intravenously.Doctor / Nurse
  • Hydrocortisone where it is used: 200 mg by slow intravenous injection or intramuscularly in an adult, 100 mg for 6–12 years, 50 mg for 6 months–6 years, 25 mg under 6 months, or 2 mg/kg to a maximum of 100 mg — unhelpful in the first hour and never a substitute for adrenaline.Doctor / Nurse
  • Refractory anaphylaxis — no improvement after two appropriate intramuscular doses: continue intramuscular adrenaline every 5 minutes while establishing something better, escalate the fluid to litres rather than millilitres, and move to a low-dose titrated adrenaline infusion by pump with continuous cardiac monitoring; an intravenous bolus of 50 micrograms (0.5 mL of 1:10 000), given slowly on a monitor, may bridge to an infusion in expert hands only.Doctor / NurseNot available at your setup — Infusion pump.
  • Second vasopressor and the beta-blocked patient: noradrenaline by infusion through central access is the appropriate second agent for refractory vasoplegia and need not be withheld until 30 mL/kg of fluid has been given; glucagon 1–2 mg intravenously or intramuscularly, repeated every 5 minutes as required (children 20–30 micrograms/kg to a maximum of 1 mg), is the specific answer to the beta-blocked patient responding poorly to adrenaline.Doctor / NurseNot available at your setup — Central venous access, Infusion pump.
  • Cardiac arrest: standard advanced life support with adrenaline 1 mg intravenously every 3–5 minutes, large-volume fluid resuscitation throughout because these patients are profoundly hypovolaemic, and a lower threshold for prolonged resuscitation since the heart is often normal and the insult reversible.Doctor / NurseNot available at your setup — Defibrillator.
  • Take timed serum tryptase samples once resuscitation is under way: sample 1 as soon as feasible (ideally within 15–60 minutes), sample 2 at 1–2 hours from symptom onset, and sample 3 as a baseline at over 24 hours — each labelled with the exact clock time of venepuncture.Doctor / Nurse
  • Observe after apparent recovery: a minimum of 6 hours from resolution of symptoms where a single dose of adrenaline produced a prompt response, extending to 12 hours or longer where the reaction was severe, more than one dose was needed, there was hypotension or airway involvement, the patient has asthma or takes a beta-blocker, the trigger is unknown or may still be absorbing, or a previous reaction was biphasic — then prescribe two adrenaline autoinjectors with the brand specified, demonstrate the technique, issue a written action plan and refer to allergy services.

Caution— what harms

  • Never give 1 mg of adrenaline intravenously — 10 mL of 1:10 000 — to a patient with a pulse: that is a cardiac arrest dose, and it causes hypertensive crisis, myocardial ischaemia, malignant arrhythmia and death; the titrated intravenous dose, for expert use only, is 50 micrograms.Doctor / Nurse
  • Never sit up, stand up or walk a hypotensive patient: this is a vasodilated, volume-depleted circulation in which up to a third of the plasma volume has left the vessels, and upright posture has itself been implicated in sudden death.
  • Never let an antihistamine, corticosteroid, nebuliser or blood test delay adrenaline — the commonest error in anaphylaxis is not an incorrect drug but a correct drug given late, and delay in giving adrenaline is one of the two consistently identified determinants of death.
  • Do not exclude anaphylaxis because there is no rash: skin change is absent in up to 10% of episodes, most often in the fastest, drug-induced intravenous reactions.
  • Do not rely on corticosteroids: they do not act within the first hour, there is no evidence they prevent biphasic reactions, steroid premedication does not protect against anaphylaxis, and reaching for them distracts from adrenaline.
  • Avoid colloids for volume replacement, particularly when a colloid may itself have been the trigger.
  • Do not push chlorphenamine in fast: rapid intravenous injection causes hypotension. NSAIDs and opiates aggravate urticaria and should be avoided for residual weals.
  • Do not sedate a patient with a threatened upper airway, and do not perform repeated blind laryngoscopy: sedation removes the tone that is keeping the airway open, and repeated attempts worsen oedema and bleeding, converting a narrowed airway into an obstructed one.Doctor / Nurse
  • Do not give glucagon to a drowsy patient without protecting the airway — it reliably causes vomiting.Doctor / Nurse
  • Do not dismiss the wheezing known asthmatic as having an asthma attack: that trap is responsible for a substantial proportion of anaphylaxis deaths, and bradycardia appearing in a shocked patient is usually pre-terminal.
  • Do not be reassured by a normal tryptase: a single value never excludes anaphylaxis, it is often unremarkable in food-triggered and normotensive reactions, and a sample without a recorded clock time is uninterpretable.
  • Do not relax observation because the patient responded promptly: about 80–90% of episodes are uniphasic but 10–20% are biphasic, returning an hour or more after apparent resolution without any further allergen exposure, and the second phase may be worse than the first.
  • Expect the harms of treatment: repeated beta-2 agonist and adrenaline dosing causes hypokalaemia, hyperglycaemia and tremor; adrenaline may precipitate hypertensive crisis, myocardial ischaemia and ventricular arrhythmia; vomiting in an obtunded patient may lead to aspiration.
  • Angio-oedema without urticaria or itch that does not respond to adrenaline is bradykinin-mediated until proved otherwise — check C4, stop any ACE inhibitor, protect the airway and treat with C1-inhibitor concentrate, icatibant, ecallantide or fresh frozen plasma; but still give adrenaline while the airway is threatened, because the mechanism cannot be determined in the first minutes and it is safe.Doctor / Nurse

Refer / escalate

Call for senior help and critical care the moment there is stridor, hoarseness, inability to swallow saliva, progressive tongue or pharyngeal swelling, hypotension, reduced conscious level, or failure to improve after two doses of intramuscular adrenaline (refractory anaphylaxis needing an adrenaline infusion and advanced airway planning) — and refer every patient who has had anaphylaxis for specialist allergy assessment before discharge.

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